Cerebellar-Thalamic Connectivity in Schizophrenia

Abstract

The literature on alterations in brain structure and function in schizophrenia, particularly in relationship to impairments in cognitive, motor, and affective functions, has made it increasingly clear that changes in the function of a single brain region cannot explain the range of impairments seen in this illness. [1][2][3][4] This realization has led to a surgence of interest in studies examining neurobiological changes in schizophrenia from the perspective of brain networks and connections among brain regions and networks, with a particular focus on neural circuits known to work together to support sensory, cognitive, and emotional processes. 5 This shift in focus is consistent with long-standing hypotheses about schizophrenia as a "dysconnection" syndrome, where impairments in cognition and behavior occur because of a failure of coordinated action across multiple brain regions. As many researchers have noted, 6 versions of this hypothesis were put forth as early as the work of Wernicke 7 and Bleuler. 8 Further, theories about abnormalities in connections among brain regions have also played a central role in more recent theories of the pathophysiology of schizophrenia. For example, one such prominent theory, put forth by Andreasen and colleagues, 9 suggested that schizophrenia involves a disruption in the integration of cortical-subcortical-cerebellar circuits, a hypothesis termed "cognitive dysmetria." Although the cognitive dysmetria hypothesis suggested the critical involvement of cerebellar, striatal, and thalamic circuits as well as cortical circuits, the majority of the work on structural and functional connectivity deficits in schizophrenia has focused on cortical and striatal dysfunction and disconnection, 10-14 with the need for additional work on the thalamus. Alterations in the structure [15][16][17] and function of the thalamus are prominent in the schizophrenia literature. 2,[18][19][20][21] As shown in anatomical studies of primates, the thalamus is topographically organized into parallel pathways connecting specific thalamic nuclei to different regions of cortex brain regions, 22 helping to form parallel loops for various types of information processing between subcortical and cortical regions. A growing number of studies have examined deficits in thalamic connectivity in schizophrenia, with several studies finding alterations in the functional connectivity between the thalamus and regions in the prefrontal in individuals with schizophrenia, 23-27 consistent with the known anatomical connectivity of the thalamus.Surprisingly few studies have examined cerebellar dysconnectivity in schizophrenia, or abnormalities in cerebellar-thalamic connections. [28][29][30][31] In part this may reflect the fact that until recently, the involvement of the cerebellum in nonmotor functions was not well-appreciated, perhaps making it a potentially less attractive target for work trying to understand the neural basis of cognitive and affective, as well as motor deficits in schizophrenia. However, there is now str...

Genetic risk factors for schizophrenia associate with sleep spindle activity in healthy adolescents

“…It has been suggested (Ferrarelli et al, ) that impairments in spindle activity in schizophrenia patients and in relatives sharing the genetic background (Manoach et al, ; Schilling et al, ) reflect deficits in thalamic‐reticular and thalamocortical mechanisms (Buchmann et al, ), representing a biological marker of schizophrenia. Functional magnetic resonance imaging (fMRI) resting‐state studies support the notion of functional abnormalities in thalamocortical circuits in schizophrenia (Barch, ), reporting reduced thalamic‐prefrontal cortex connectivity (Anticevic et al, ; Woodward, Karbasforoushan, & Heckers, ) as well as enhanced thalamic‐sensory motor cortices connectivity (Anticevic et al, ; Klingner et al, ; Woodward et al, ), which correlated with symptom severity in a longitudinal fMRI study (Anticevic et al, ). Furthermore, in the longitudinal fMRI resting‐state study, thalamic connectivity abnormalities predated the onset of schizophrenia (Anticevic et al, ).…”

Cognition and resting-state functional connectivity in schizophrenia

“…Working memory processes encompass the ability to temporarily store and manipulate information “on-line” and given its relationship to the functioning of the dlPFC, is closely linked with executive functioning ability (for review, see Barch & Sheffield, 2014). Due to such reliable impairments in working memory in schizophrenia, five studies assessed its relationship with functional connectivity.…”

“…In addition, abnormalities in the cerebellum have also been observed in schizophrenia, with evidence of white matter abnormalities within certain cerebellar lobes (Kim et al, 2014), as well as abnormal size and decreased blood flow in the cerebellum during a broad range of cognitive tasks (Andreasen et al, 2008; Barch, 2014). Importantly, reduced functional connectivity between the cerebellum and medial dorsal nucleus of the thalamus has been observed in schizophrenia, providing evidence of abnormalities in this portion of the CCTCC as well (Anticevic et al, 2014; Collin et al, 2011).…”

Practice and Learning: Spatiotemporal Differences in Thalamo-Cortical-Cerebellar Networks Engagement across Learning Phases in Schizophrenia

“…Consistent with the model, the SZ group did not transition to a brain–accuracy network that engaged key subcortical, thalamic, and cerebellar regions as in the high-performing controls with the best working memory capacities. Evidence is accumulating for the thalamus as a key node in this brain–learning network in SZ (54). Studies have demonstrated thalamic hypoconnectivity between frontal and striatal regions and hyperconnectivity in sensory, somatosensory, and motor regions in chronic, early, and at-risk for SZ groups (55–58).…”